This invention relates in vivo optical measurements, including but not limited to spectroscopy, incorporated in catheter-based implementations.
For intravascular optical measurements to be made reliably, various background factors and artifacts may need to be normalized or referenced. This includes factors and artifacts that exist or occur before and during the optical measurements.
Obtaining in vivo intravascular readings can be a difficult task. The environment is very harsh and not conducive to precise, reproducible optical measurements. First, the presence of blood, which is both highly scattering and absorbing, raises significant hurdles. The blood can vary in optically significant factors such as hematocrit (which varies scattering) and cholesterol content (which varies absorption), which can cause major variances in optical measurements from patient to patient.
Second, intravascular measurements can also be complicated by motion artifacts. This includes not only blood flow, but also cardiac motion in the case of coronary measurements. This motion can induce significant variances, for instance, in the output of a fiber delivery light to the distal end of catheter. These variances must be determined before accurate measurements can be made.
Finally, catheter technologies require complex, microscopic manufacturing processes that make it hard to provide exactly reproducible readings from catheter to catheter.
The invention provides methods and apparatus to reference or normalize optical measurements, by removing or accounting for background factors and artifacts, such as motion artifacts. The invention provides methods for referencing factors due to equipment that can be addressed prior to use of an optical catheter, as well as factors due to the local measurement conditions in a patient that arise during use. Some of these factors are the same from patient to patient, such as the general nature of blood, and others vary from patient to patient, such as the specific constituents of each patient""s blood.
In general, in one aspect the invention features an apparatus for calibrating an optical catheter. The apparatus includes a hollow well with a reflective internal surface; an entrance (and optionally an exit opening) arranged at a proximal end of the hollow well for inserting a catheter; and a sealing structure arranged in the entrance to contact the catheter during use to inhibit external light from entering the hollow well. The reflective internal surface can include a diffuse or direct reflective material. The apparatus can also include sealing structures arranged in the entrance and exit openings to contact the catheter during use to inhibit external light from entering the hollow well.
In another embodiment, the invention includes an apparatus for measuring back-reflection from the distal tip of an optical catheter that includes a beam sampler arranged to transmit a beam of electromagnetic radiation, e.g., visible light, from an electromagnetic radiation source, such as a laser, to the catheter and to receive and divert polarized electromagnetic radiation reflected from a proximal end of the catheter and unpolarized electromagnetic radiation back-reflected from the distal tip of the catheter; an optical redirector, e.g., a mirror or prism, arranged to direct polarized reflected electromagnetic radiation and unpolarized back-reflected electromagnetic radiation from the beam sampler to a polarizer; a polarizer arranged to selectively transmit unpolarized back-reflected electromagnetic radiation and block polarized reflected electromagnetic radiation; and a detector arrange to receive the unpolarized back-reflected electromagnetic radiation.
In another aspect, the invention features a method of generating a reference signal to normalize optical in vivo intravascular measurements for characteristics of a specific catheter by inserting a catheter into an environment comprising known optical characteristics; transmitting electromagnetic radiation through the catheter into the known environment; receiving and transmitting through the catheter any electromagnetic radiation reflected from the known environment; and processing the reflected electromagnetic radiation transmitted through the catheter to generate a reference signal that is specific for characteristics of the catheter. The method can be conducted prior to and/or after a catheterization procedure.
In these methods, the known environment can be a new reflecting apparatus as described herein including a hollow well and a reflective internal surface. The known environment can also be a liquid having known optical characteristics, such as scatter and absorbance. For example, the liquid can include styrene divinyl/benzene cross-linked copolymer beads suspended in an ultrapure aqueous solution. The new methods can be conducted when or after the catheter is manufactured, and the reference signal can be transcribed into computer-readable data or optically readable symbols.
In another aspect, the invention includes a method for normalizing optical in vivo intravascular measurements for variances in catheter output at the distal tip by transmitting electromagnetic radiation, e.g., light, from a source into the catheter; receiving electromagnetic radiation back-reflected from the distal tip of the catheter and transmitted through the catheter; processing the back-reflected electromagnetic radiation transmitted through the catheter to generate a reference signal specific for the back-reflected electromagnetic radiation; obtaining an actual in vivo intravascular measurement; and normalizing the actual measurement for variances in catheter electromagnetic radiation output at the distal tip by processing the actual measurement with the reference signal.
In one embodiment of this method, the electromagnetic radiation is polarized light, and the method further includes receiving polarized light reflected from a proximal end of the catheter; receiving unpolarized light back-reflected from the distal tip of the catheter; and removing the polarized reflected light from the unpolarized back-reflected light before processing the back-reflected light. The method can be conducted during a catheterization procedure, and processing can involve taking the ratio of the actual measurement over the reference signal, or subtracting the reference signal from the actual measurement.
The invention also features a method for normalizing an optical in vivo intravascular measurement in a patient by obtaining a catheter; illuminating a portion of the patient""s blood with electromagnetic radiation emitted from the catheter; receiving electromagnetic radiation reflected from the blood; processing the reflected electromagnetic radiation to generate a reference signal that is specific for characteristics of the blood; taking an actual in vivo intravascular measurement in the patient; and normalizing the actual measurement by processing the actual measurement with the reference signal. In this method, the portion of the patient""s blood can be in a blood vessel, wherein the method is conducted during a catheterization procedure. The portion of the patient""s blood can also be in a container, wherein the method is conducted before and/or after a catheterization procedure. In these methods, the reference signal can be specific for, e.g., one or more of blood hematocrit and cholesterol.
In another aspect, the invention features a method for normalizing optical in vivo intravascular measurements in a patient by obtaining a catheter; illuminating a portion of vasculature in the patient with electromagnetic radiation emitted from the catheter; receiving electromagnetic radiation emitted from the portion of vasculature; processing the emitted electromagnetic radiation to generate a reference signal that is specific for characteristics of the portion of vasculature; taking an actual in vivo intravascular measurement in the patient; and normalizing the actual measurement by processing the actual measurement with the reference signal. In these methods, the portion of vasculature can be normal or diseased vasculature, e.g., vasculature that has a vascular disease other than lipid-rich, vulnerable atherosclerotic plaque, such as fibrous, stable atherosclerotic vasculature. These methods can be conducted before and/or after a catheterization procedure.
All of these new methods can be used individually or in combinations of any two or more methods. Similarly, the new apparatus can be used individually or in conjunction with each other. In addition, the invention features methods of obtaining reference measurements of the various components of the materials through which electromagnetic radiation travels from a catheter to the tissue, into the tissue, and back to the catheter to enhance the ability to discriminate measurements from the target.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.